We propose a series of experiments to further elucidate the possible role of hormones as one important set of controllers contributing to human behavior. We plan to examine the interrelationships of affect state (especially depression and anxiety) and hormonal function. A major aim is to attempt the difficult separation of two clinically important and common affect states, depression and anxiety, by careful repetitive clinical observaion plus psychological testing using self rate and trained observer rating scales, and by the pharmacological use of anxiolytic drugs. The individual affect states of depression and anxiety will then be correlated with plasma, urine, and cerebral spinal fluid levels of ACTH, cortisol, growth hormone, and(in males) testosterone, during depression or anxiety and after recovery. We plan to explore the effect of drugs which influence noradrenergic and dopaminergic CNS neurons controlling neuroendocrine function. Specifically, the effect of L-DOPA, D- amphetamine, L-amphetamine, and alpha-methyl-para-tyrosine (AMPT), alone or in various combinations, will be used to accelerate synthesis, increase release and block uptake, or block synthesis of transmitter substances in depressed and recovered patients. Behavioral and hormonal changes induced by these drugs will be correlated. The value of cortisol response to dexammethasone as a predictor of subsequent response to antidepressant medication will be examined. We propose also to study the effects of atlered levels of ACTH and cortisol on human behavior, since these two "peripheral" hormones are known to have effects on animal behavior. Altered hormonal levels will be produced directly by treatment with these hormones or by altering their synthesis and release. Last, a series of experiments is aimed at characterizing in further detail the abnormal function of the hypothalamic-pituitary- adrenocortical system that we have previously described in affective illness, with special attention to the effect of novelty situation (hospitalization) and by the technique of psychological examination of depressed and anxious persons at home prior to hospitalization.